Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline

The male germline transcriptome changes dramatically during the mitosis-to-meiosis transition to activate late spermatogenesis genes and to transiently suppress genes commonly expressed in somatic lineages and spermatogenesis progenitor cells, termed somatic/progenitor genes. These changes reflect epigenetic regulation. Induction of late spermatogenesis genes during spermatogenesis is facilitated by poised chromatin established in the stem cell phases of spermatogonia, whereas silencing of somatic/progenitor genes during meiosis and postmeiosis is associated with formation of bivalent domains which also allows the recovery of the somatic/progenitor program after fertilization. Importantly, during spermatogenesis mechanisms of epigenetic regulation on sex chromosomes are different from autosomes: X-linked somatic/progenitor genes are suppressed by meiotic sex chromosome inactivation without deposition of H3K27me3. Our results suggest that bivalent H3K27me3 and H3K4me2/3 domains are not limited to developmental promoters (which maintain bivalent domains that are silent throughout the reproductive cycle), but also underlie reversible silencing of somatic/progenitor genes during the mitosis-to-meiosis transition in late spermatogenesis. 29 samples analyzed by ChIP-Seq

在有丝分裂向减数分裂转换（mitosis-to-meiosis transition）过程中，雄性生殖系转录组（male germline transcriptome）会发生显著动态变化，以激活精子发生后期基因，并瞬时抑制通常在体细胞谱系（somatic lineages）与精子发生祖细胞（spermatogenesis progenitor cells）中表达的基因——这类基因被定义为体细胞/祖细胞基因（somatic/progenitor genes）。此类变化反映了表观遗传调控（epigenetic regulation）的核心作用。精子发生进程中，精子发生后期基因的诱导有赖于精原细胞干细胞阶段建立的 poised染色质（poised chromatin）；而在减数分裂及减数分裂后阶段，体细胞/祖细胞基因的沉默则与二价结构域（bivalent domains）的形成密切相关，这类结构域同时可保障受精后体细胞/祖细胞程序的恢复。尤为关键的是，精子发生过程中性染色体的表观遗传调控机制与常染色体（autosomes）存在显著差异：X连锁的体细胞/祖细胞基因通过减数分裂性染色体失活（meiotic sex chromosome inactivation）实现沉默，且不会发生H3K27me3的沉积修饰。本研究结果显示，携带H3K27me3与H3K4me2/3修饰的二价结构域，并非仅局限于在整个生殖周期中维持沉默状态的发育启动子（developmental promoters），同时也是精子发生后期有丝分裂向减数分裂转换过程中，体细胞/祖细胞基因可逆性沉默的分子基础。本研究通过ChIP-Seq对29份样本开展了分析。